This study investigated the prevalence of insulin promoter factor-1(IPF-1) mutations in familial early-onset diabetes mellitus in Trinidad. We screened 264 unrelated subjects with type 2 diabetes diagnosed before 40 yr of age and a family history of diabetes for mutations in the minimal promoter and coding region of the IPF-1 gene (IPF1). This study population included 169 patients of East Indian descent (Indo-Trinidadians), 66 of African descent (Afro-Trinidadians), and 29 of mixed ancestry. We identified five IPF1 variants, including one new missense mutation E224K, the previously described diabetes-associated duplication P242 P243dupP, two silent mutations in the codons for Leu54 (c.162G>A) and Ala256 (c.768C>A), and a substitution in the 5'-untranslated region (c.-18C>T). The E224K mutation was found in two unrelated diabetic Indo-Trinidadians and 0 of 60 controls. It was present on the same haplotype in both patients suggesting a founder effect. The E224K mutation cosegregated with early-onset diabetes or impaired glucose tolerance in a large family, suggestive of the type 4 form of maturity-onset diabetes of the young rather than type 2 diabetes. Functional studies of E224K showed reduced transactivation activity. IPF1 mutations leading to synthesis of a mutant protein may contribute to the development of familial early-onset diabetes/maturity-onset diabetes of the young in Indo-Trinidadians.
General harmonic and hybrid orbital force fields have been calculated for methyl chloride, bromide and iodide using the best available frequency, Coriolis coefficient, and centrifugal distortion data, including the recent laC frequencies for the chloride and iodide. Anharmonicity corrections were made to the fundamental frequencies using Dennison's rule and x values of 0"04 for CH stretching, 0"02 for CH bending, and 0"01 for CX stretching modes. These were the most reasonable values which did not seriously over-compensate for the product rule deficiencies in the 12C and 1~C frequencies.The 13C and CDaX frequency information was input in the form of frequency shifts from the 12CHaX frequencies. All 12 parameters in the most general harmonic force fields are determined with significance for the first time, although the previously uncertain parameters F12 and F13 are only determined with good precision when the 13C frequency data are utilized in addition to the other information. The signs of Fx2, F45 and F46 are in agreement with the predictions of the hybrid orbital model, which are quantitatively obeyed more closely in methyl iodide than in methyl bromide or chloride.There is a slight incompatibility between the centrifugal distortion data and the 13C frequency shifts in the A1 species, attributed here to the unknown effects of higher-order terms on the distortion constants.The effect of using the best present estimate of the equilibrium CH bond length, re(CH) = 1 "085 3,, instead of the previous estimate of re= 1 "095 h, is considered and the changes in the force constants listed.
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